<h3>Introduction</h3> ARS-1, an intranasal (IN) epinephrine spray, is under development as a needle-free alternative to manual intramuscular (IM) injection and epinephrine injection devices for allergic reactions. <h3>Methods</h3> A two-part, single- and repeat-dose, randomized, crossover, phase 1 study of ARS-1 (2.0 mg), epinephrine auto-injector (0.3 mg), and IM injection (0.3 mg) was conducted in healthy volunteers. Pharmacokinetic (PK) and pharmacodynamic (PD) parameters were examined. IRB approval was obtained for this study. <h3>Results</h3> Forty-two subjects were included. Following single dose, mean C<sub>max</sub> values were 753, 481, and 339 pg/mL for auto-injector, ARS-1, and IM injection, respectively. Median t<sub>max</sub> (minutes) was shortest for auto-injector (7.5), then ARS-1 (30), and IM injection (45). After repeat dosing, PK characteristics were similar for ARS-1 and auto-injector. C<sub>max</sub> was 992 and 1000 pg/mL for both ARS-1 treatments (right/right and left/right naris), median t<sub>max</sub> 30 minutes, and 840 pg/mL for auto-injector (left/right thigh), median t<sub>max</sub> 15 minutes. After single dose, PD responses were greater for ARS-1 compared with auto-injector and IM injection. Mean systolic blood pressure, diastolic blood pressure, and heart rate E<sub>max</sub> values, respectively, were greater for ARS-1 (23.6 mmHg, 8.1 mmHg, and 17.3 bpm) versus auto-injector (18.2, 5.62, and 12.3) and IM injection (11.9, 5.48, and 9.71). After repeat dosing, ARS-1 improved PD responses versus auto-injector and IM injection. <h3>Conclusion</h3> PK parameters of single dose ARS-1 single were bracketed by IM injection and auto-injector, with repeat dosing similar to auto-injector. ARS-1 (single and repeat dosing) PD parameters were superior to auto-injector and IM injection.